Human PERP blocking peptide

Objective: The integration of proprioception with vision, touch or audition is considered basic to the developmental formation of perceptions, conceptual objects and the creation of cognitive schemes. Thus, mapping of proprioceptive information processing is important in cognitive research. A stimulus of a brisk change of weight on a hand held load elicit a proprioceptive evoked potential (PEP). Here this is used to examine early and late information processing related to weight discrimination by event related potentials (ERP). Methods: A gating paradigm having 1 s between the proprioceptive stimuli of 100 g weight increase was recorded in 12 runs of 40 pairs and an 1:4 oddball task of discriminating between 40 and 100 g weight increase was both recorded in 24 healthy men. The subjects were stratified in 3 groups according to their discrimination errors. Results: The proprioceptive event related potential (PERP) consisted of a contralateral parietal P60, frontal N70, midline P100, initial contralateral later widespread N160, vertex P200, parietal N290 and target related widespread P360 and posterior N500. The target related components were augmented in the best performers, while the bad performers had delayed P60 and attenuated N70. The amplitudes of N160, P200 and N290 were unrelated to performance. Gating was seen as attenuation of P100, N160 and P200 amplitude. Conclusions: The proprioceptive stimulus feature processing seem to be accomplished in the first 100 ms, while later components are modified by context as expected from previous findings in the somatosensory modality. Significance: The PERP could be a useful research tool in the investigation of bodily information processing in neuropsychiatric disorders. (c) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Erythrokeratoderma (EK) is heterogeneous clinical entity characterized by excessive scaling with resulting erythrokeratotic plaques. Several genes have been linked to EK and they encode a number of proteins that are important for the integrity of the keratinocyte layer of the epidermis. PERP is a transcription factor that is activated by both p53 and p63. However, its deficiency in a mouse model appears to only recapitulate p63-mediated role in skin development and organization. We report an extended multiplex consanguineous family in which an EK phenotype with a striking similarity to that observed in Perp(-/-) mice, is mapped to an autozygous region on chromosome 6 that spans PERP. Whole-exome sequencing revealed a novel variant in PERP that fully segregated with the phenotype. Functional analysis of patient- and control-derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible. Our results, therefore, support the establishment of an autosomal recessive PERP-related EK phenotype in humans.